tbuckley/cabot-search huggingface dataset:
Real-world outcomes among patients with metastatic colorectal cancer treated first line with bevacizumab-awwb.
Authors: Ran Jin, Adesuwa S. Ogbomo, Neil A. Accortt, Lincy S. Lal, Geetanjali Bishi, Darcie Sandschafer, Jerome H. Goldschmidt
Journal: Journal of Clinical Oncology (2022)

e15581 Background: Bevacizumab-awwb (MVASI) was the first FDA-approved biosimilar to Avastin (reference product, RP). Real-world data on effectiveness and safety remain limited and may help address barriers to utilization. Methods: Adult patients who had a confirmed diagnosis of metastatic colorectal cancer (mCRC) (initial presentation on or after 1 January 2018) and initiated bevacizumab-awwb between 19 July 2019 and 30 April 2020 were identified in the ConcertAI Definitive Oncology EMR Dataset. A retrospective medical chart review was conducted to evaluate patient clinical characteristics and outcome data. The current analysis focused on the subset of patients who initiated first-line (1L) bevacizumab-awwb containing therapy (with no prior use of RP) to evaluate incidence of events of interest (EOIs) (Table) and overall survival (OS) probability using Kaplan-Meier analysis. Patients were followed from the initiation of 1L therapy until death, end of record, or end of study period (June 2021), whichever occurred first. Results: A total of 129 patients who initiated bevacizumab-awwb as 1L treatment in combination with chemotherapy were included in this analysis. Majority of patients (78.3%) were treated at clinical oncology practices in a community setting (median age: 60.5 years, 53.5% male). 34.9% of patients had non-metastatic disease (stage of I/II/III) at the initial diagnosis and 38.8% had undergone surgical resection. Median duration of available follow-up data was 10.7 (range: 0.69-22.4) months. During the study period, 100 out of 129 patients had disease progression of which 46 patients had a record of death. The Kaplan-Meier analysis showed that 12-month OS probability was 71.4% (95% CI: 61.0%-79.5%). During treatment with bevacizumab-awwb, 20 EOIs were reported in 18 patients (14.0%). Distribution of events and their management are presented in the Table. None of these EOIs resulted in death. Conclusions: Biosimilar bevacizumab-awwb appeared to be well tolerated, with observed EOIs being manageable, and 12-month OS probability of &gt; 70% for treating patients with mCRC in the real-world setting.[Table: see text]
Study on the efficacy and safety of sintilimab combined with nab-paclitaxel as second-line treatment for advanced or metastatic gastric cancer (GC)/ gastroesophageal junction (GEJ) cancer.
Authors: Jianzheng Wang, Yunduan He, Baiwen Zhang, Xiaojiao Cheng, Qingli Li, Huifang Lv, Caiyun Nie, Beibei Chen, Weifeng Xu, Jing Zhao, Shuiping Tu, Xiaobing Chen
Journal: Journal of Clinical Oncology (2022)

e16016 Background: Advanced gastric cancer has poor prognosis and short survival period. Anti-PD-1 antibodies have shown some efficacy in second-line treatment of advanced or metastatic GC/GEJ cancer, but were not superior to monotherapy. The combination of chemotherapy and anti-PD-1 antibody has been proved to have synergistic effect. Nab-paclitaxel is one of the most commonly used second-line regimens in China. Therefore,we aimed to evaluate the efficacy and safety of sintilimab combined with Nab-paclitaxel in the treatment of advanced GC/GEJ cancer patients. Methods: We retrospectively analyzed patients with advanced GC/GEJ cancer that progressed after first line systemic therapies and treated with sintilimab combined with Nab-paclitaxel from April 1, 2019 to December 31, 2021. The primary end point was progression free survival (PFS). Secondary end points included objective response rate (ORR), disease control rate (DCR), and safety. Results: Thirty-nine patients were enrolled and eligible for response assessment. Complete response (CR) was not observed, 15 patients achieved partial response (PR), 16 patients had stable disease (SD) and 9 patients had progression disease (PD). The ORR and DCR were 15 (38.5%) and 31 (79.5%), respectively. Median PFS was 5.4 months (95%CI: 3.072-7.728). We further analyzed PFS between different subgroups of chemoimmunotherapy regimens in order to find which patients could benefit more. Firstly, The PFS of HER2 positive and HER2 negative patients was 7.1months (95%CI:3.367-10.833) and 5.3 months (95%CI:4.018-6.582), respectively (p = 0.947). The median PFS of PD-L1 positive, PD-L1 negative and PD-L1 unknown patients was 5.3months (95%CI:3.744-6.856), 8.1months(95%CI:3.371-12.829) and 6.1 months(95%CI:2.649-9.551)(p = 0.918). Finally, we analyzed the effect of chemoimmunotherapy cycles on PFS. The results showed that PFS of &gt; 4 cycles was numerically longer than that of ≤ 4 cycles, and PFS were 7.1 months (95%CI:4.378-9.822) and 5.2months (95%CI:3.091-7.309)(p = 0.424), respectively. Most of the adverse events (AEs) were grade 1-2.The most common treatment-related adverse events (TRAEs) of grade 3-4 were anemia 5(12.8%), neutropenia 5(12.8%), leukopenia 4(10.3%). The potential immune-related adverse events (irAEs) were grade 1 pneumonia 1(2.6%). Only one patient developed grade 4 hepatitis (2.6%). Conclusions: These results indicated that sintilimab combined with Nab-paclitaxel exhibited good anti-tumor activity and acceptable safety profile as second-line treatment for advanced or metastatic gastric cancer. These results warrant further accrual and evaluation and explore which patients can benefit more from the combined treatment strategy.
Changing recognition of breast cancer–related leptomeningeal disease and response to therapy: A retrospective single institution review.
Authors: Gerald Carter Wallace, Kamran A. Ahmed, Aixa Elena Soyano Muller, Peter A. J. Forsyth
Journal: Journal of Clinical Oncology (2022)

2027 Background: Breast cancer related leptomeningeal disease (BC-LMD) is a dire diagnosis for 5-8% of breast cancer patients with overall survival (OS) measured in weeks without treatment. As new treatments prolong survival with breast cancer, the risk of developing BC-LMD may be increasing. We hypothesized that the rate of BC-LMD diagnosis increased significantly with time. We also predicted that OS with BC-LMD had changed with time and in relationship to molecular subtype and treatment following BC-LMD diagnosis. Methods: With approval of the local Scientific Research Committee and IRB, we conducted a retrospective analysis of medical records for patients treated or diagnosed with breast cancer at MCC from 2011-2020. Patient demographics, tumor characteristics, treatments, and outcomes were collected. Kaplan Meier survival curves were used to determine median overall survival (OS), progression of disease, and differences by molecular subtype. Univariate and multivariate analyses were used to determine characteristics of primary tumors and treatments which affected OS. Results: Of the 133 cases identified, significantly more were diagnosed between 2016-2020 than 2011-2015 (p &lt; 0.01). Significant increases were seen in HER2+ and TNBC patients (p &lt; 0.05) but not for ER/PR positive (HR+) disease (p = 0.058). HER2+ LMD associated with longest overall survival (OS; 7mths) followed by HR+ disease (3mths) and TNBC with the shortest OS (2mths). Systemic metastases preceded BC-LMD diagnosis in 72% of cases and CNS metastases in 85% of cases. HER2+ disease also conferred increased survival after CNS metastases were diagnosed until progression to LMD (8mth vs 2mth for HR+ and 1mth for TNBC LMD; p &lt; 0.05). Positive impact on survival by HER2 targeted therapies may account for improved OS in this population. Other factors which increased OS generally were: WBRT, continuation of systemic therapy, delivery of intrathecal chemotherapy, and participation in clinical trials. Having TNBC and decision to defer treatment were associated with reduced OS. Conclusions: This study highlights the importance of identifying patients with BC-LMD early and with the intention to treat. Prospective clinical trials and population-based studies are needed to advance treatment of BC-LMD.
Nurse navigator–initiated geriatric assessments in hematology/oncology clinics.
Authors: John L. Shaia, Raymond Liu, Hongxin Sun, Tatjana Kolevska, Dinesh Kotak, Kate Belohlav, Grant Richard Williams, Amit Arora
Journal: Journal of Clinical Oncology (2022)

12051 Background: As the number of older adults with cancer continues to grow, there is an urgent and unmet need to implement geriatric assessments and toxicity screening tools (G8 and CARG toxicity tool) for patients 65 and older with a cancer diagnosis in real-world settings. Studies of these tools show completion rates of 20-35% when administered by a physician. To determine if nurse navigators could increase completion rates, we implemented a pilot in seven community cancer centers within an integrated health system. Methods: A pilot project of G8 and CARG toxicity tool implementation was completed at seven community cancer centers from May 1,2021 to December 31,2021 in patients age ≥ 65 years, with solid or malignant hematologic cancer diagnosis. G8 was administered at seven sites and CARG was assessed in addition to G8 on solid tumor patients undergoing chemotherapy at four of the seven sites. Referrals to nutrition, audiology, physical therapy, psychiatry, and neurology were sent by nurse navigators based on assessment results. Results: The total number of eligible patients for G8 was 1372, with 1082 (78.9 %) successfully completing assessment, and the total number of eligible patients for CARG toxicity tool was 563 with 516 (91.6%) successfully completing assessment. The median age of patients completing assessment was 74 years old (range 65-100) and 52% were female. The cohort included Asian / Pacific Islanders (23%), Black (15%), Hispanic White (8%), and Non-Hispanic Whites (51%). Most common cancers included genitourinary cancer (18%), breast cancer (17%), upper GI cancer (15%), and thoracic cancer (13%). The assessments resulted in referrals to multiple services including nutrition (193 referrals), audiology (30), physical therapy (18), psychiatry (5), and neurology (5). Conclusions: Nurse navigators can successfully implement G8 and CARG toxicity tool in hematology-oncology clinics in a broad range of cancer types at a high rate with resultant referrals to multiple supportive services in real-world settings.
Systematic analysis the genomic and microenvironment characteristics with the status of human leukocyte antigen (HLA) and the integration of HLA LOH, TMB and PD-L1 could further distinguish the responders to immunotherapy.
Authors: Xiaotao Zhang, Jun Wang, Jun Chen, Linlin Zhang, Yaping Guan, Huili Chu, Haiming Yu, Lan Yu, Huiping Lu, Haoxuan Jin, Tiantian Gu, Xiuyan Wang
Journal: Journal of Clinical Oncology (2022)

e20529 Background: Although studies have shown that loss of heterozygosity (LOH) at the human leukocyte antigen (HLA) locus is one of the mechanisms of immune escape, the effect of HLA LOH on the immune checkpoint inhibitors (ICIs) treatment is still need to be further investigated, especially for the patients with positive programmed cell death-Ligand 1 (PD-L1) expression and high tumor mutation burden (TMB). Methods: 425 sample of Chinese lung cancer patients who received PD-L1 immunotherapy were performed with targeted panel sequencing to analyzed the genomic characteristics with HLA status. 994 non-small cell lung cancer (NSCLC) sample from The Cancer Genome Atlas (TCGA) were used to analyze the impact of HLA LOH on the tumor microenvironment. In addition, 89 samples from previous study were used to analyze the association of HLA status with the ICIs treatment in NSCLC. Results: The genomic characteristics from 425 sample of Chinese lung cancer patients who received PD-L1 immunotherapy were analyzed. We found that mutation frequency of driver genes and TMB in the HLA LOH high group were significantly increased. Transcriptome analysis revealed HLA LOH played a critical role in the tumor immune microenvironment in PD-L1 + /TMB-H population and the impact on lung adenocarcinoma was greater than that on lung squamous cell carcinoma. Progression-free survival of PD-L1 + /TMB-H population was significantly decreased in HLA LOH group which suggest that comprehensive considering HLA LOH as a biomarker may improve clinical response to immunotherapy. Conclusions: This work showed the genomic and immune microenvironment characteristics of HLA LOH and demonstrated HLA LOH as a significant negative predictor of outcomes after ICIs treatment, especially in PD-L1 + /TMB-H population. These data suggested that comprehensive considering HLA LOH as a biomarker may improve clinical response to immunotherapy.
TACTI-003: A randomized phase IIb study of eftilagimod alpha (soluble LAG-3 protein) and pembrolizumab as first-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma.
Authors: Douglas Adkins, Valerii Cheshuk, Julio Antonio Peguero, John J. Park, Antonio Lopez-Pousa, Willem Lybaert, Irene Brana, Bernard Doger, Frederic Triebel
Journal: Journal of Clinical Oncology (2022)

TPS6099 Background: Eftilagimod alpha (efti) is a soluble LAG-3 protein targeting a subset of MHC class II molecules that mediate antigen presenting cell (APC) and CD8 T-cell activation. Data from a non-randomized, phase II trial of efti plus pembrolizumab (TACTI-002) showed encouraging antitumor activity and manageable safety when given as second-line treatment of patients with recurrent or metastatic head and neck squamous-cell carcinoma (RM-HNSCC). TACTI-003 (NCT04811027) is a multicenter, open label, randomized phase IIb trial to investigate efti plus pembrolizumab in the first-line setting for RM-HNSCC. Methods: A total of 154 patients (pts) are currently being recruited into two cohorts (A+B). In cohort A, pts with tumors that are CPS≥1 will be randomly assigned 1:1 to receive either efti (30 mg subcutaneously Q2W for initial 6 months, thereafter Q3W) plus pembrolizumab (400 mg intravenously Q6W) for up to two years or pembrolizumab alone. Randomization will be stratified by CPS (1-19 vs. ≥ 20) and ECOG PS (0 vs. 1). Pts with tumors that are CPS &lt; 1 will receive efti plus pembrolizumab (cohort B). Imaging will be performed every 9 weeks. The primary endpoint (EP) is objective response rate (ORR) by RECIST1.1. Secondary EPs include overall survival, ORR according to iRECIST, time to and duration of response, disease control rate, progression-free survival, occurrence of anti-efti -specific antibodies, safety, and quality of life. Exploratory endpoints comprise biomarkers. The study has been approved by relevant competent authorities, ethic committees and IRBs. Clinical trial information: NCT04811027.
Phase II study of ceralasertib (AZD6738) in combination with durvalumab in patients with advanced gastric cancer.
Authors: Minsuk Kwon, Seung Tae Kim, Jung Yong Hong, Gahyun Kim, Simon Smith, Peter G. Mortimer, Bienvenu LoembE, Emma Dean, Won Ki Kang, Jeeyun Lee
Journal: Journal of Clinical Oncology (2022)

4045 Background: Alterations in DNA damage response (DDR) and repair are associated with genomic instability and increased somatic tumor mutational burden, and modulating DNA repair using specific inhibitors is a promising strategy to boost the efficacy of cancer immunotherapy. Ceralasertib is an oral inhibitor of the serine/threonine protein kinase Ataxia Telangiectasia and Rad3 Related (ATR), which is crucial to the cell’s response to replication stress. Methods: This phase 2 trial was designed to evaluate the efficacy and safety of ceralasertib in combination with durvalumab in patients with advanced gastric cancer (AGC). The study drug regimen was ceralasertib 240 mg BD days 15 to 28 in a 28-day cycle in combination with durvalumab at 1500 mg day 1 every 4 weeks. The primary end point was overall response rate (ORR) by RECIST (v1.1). Exploratory biomarker analysis was performed using fresh tumor biopsies in all enrolled patients. Results: 31 patients (median no. of prior lines, 2; range, 2-5) were enrolled between Jul 2019 and Mar 2020. All enrolled patients had confirmed microsatellite stable tumors, 5 patients were EBV positive, and 24 patients were PD-L1 positive (CPS≥1). Two patients had received prior anti-PD-1 treatment. At the time of data cut-off (Dec 2020), 30 patients were evaluable for response: 7 partial responses (one patient with prior anti-PD-1 treatment), 11 stable disease, and 12 disease progression were observed. The ORR was 22.6%, DCR 58.1 %, median PFS 3.0 months (95% confidence interval (CI), 2.1-3.9), median duration of response 5.7 months (95% CI, 4.9-6.5), and median OS was 6.7 months (95% CI, 3.8-9.6). A subgroup of patients (n = 11) who with loss of ATM expression and/or high proportion of mutational signature attributable to homologous repair deficiency (sig. HRD) demonstrated significantly longer PFS than those (n = 12) who had intact ATM and low sig. HRD (5.60 vs 1.65 months, hazard ratio 0.13, 95% CI 0.045-0.39, long-rank P &lt; 0.001). The most common adverse events of any grade were fatigue (n = 22, 71.0%), nausea (n = 20, 64.5%) and anorexia (n = 19, 61.3%), and the most common adverse events of grade 3 or more were anemia and thrombocytopenia (n = 11, 35.5% each). Conclusions: Ceralasertib in combination with durvalumab demonstrated promising anti-tumor activity with durable responses in refractory AGC. Clinical trial information: NCT03780608.
Co-occurring alterations across molecular pathways in metastatic colorectal cancer (mCRC).
Authors: Alex John Liu, Daniel Walden, Syeda Mina, Blake Langlais, Leylah Drusbosky, Dong Yang, Jason S. Starr, Jeremy Clifton Jones, Tanios S. Bekaii-Saab, Daniel H. Ahn, Mohamad B. Sonbol
Journal: Journal of Clinical Oncology (2022)

3590 Background: Co-occurring alterations (COAs) in the HER2 and MAPK pathway are rare in mCRC. RAS, HER2 and BRAF alterations have been associated with resistance to EGFR inhibitor therapy (EGFR-mab). Typical co-occurring mutually exclusive gene mutations such as in KRAS and BRAF have been reported. This study aims to evaluate the prevalence of co-occurring alterations in the MAPK pathway or across MAPK/ HER2 and correlate to outcomes in patients with mCRC treated with EGFR-mab. Methods: This is a retrospective study of patients with mCRC within the Mayo Clinic database who have available blood-based NGS Guardant 360 data (September 2017-November 2021) and contained co-alterations in the MAPK pathway or across MAPK/ HER2. MSI-high cases were excluded. Typical-RAS was defined as alterations in codons 12, 13, 59, 61, 117, and 146 of KRAS, HRAS, and NRAS. Atypical-RAS alterations were considered mutations at other codons of these genes. Patient characteristics, specific mutations, and outcome data were assessed. Results: 692 patients (pts) with mCRC were identified and 66 (9.5%) of those had COAs detected. 59/66 pts had clinical data available. Median age was 52 years, 55.9% were male, and 61.0% had left-sided tumors. The frequency of detected alterations was: BRAF-V600E (7.3%), BRAF-non-V600E (7%), BRAF-amplification (3.04%), RAS-typical (39.5%), RAS-atypical (2.1%), HER2 amp (0.5%), HER2-mutation (1.2%) and PIK3CA (13%). COAs are described in the table. Twenty-three pts received EGFR-mab; COAs developed in 19 of them after progression on EGFR-mab. Four pts received EGFR-mab with documented COAs at baseline with none of them responding to treatment. Conclusions: COAs in MAPK and MAPK/ HER2 pathway are not uncommon in pts with mCRC emphasizing on the importance and feasibility of blood based NGS vs. selected gene testing. In pts with prior EGFR-mab treatment, COAs were detected after progression on treatment in the majority of pts, suggesting a mechanism of secondary treatment resistance. Further data including prospective validation is warranted. [Table: see text]
Greater expression of THBS2 and VACN in gastric carcinoma compared to gastritis.
Authors: Zhisong Fan, Li Feng, Linnan Liu, Dan Li, Jiayin Liu, Jing Zuo, Yudong Wang, Jing Han, Xue Zhang, Long Wang
Journal: Journal of Clinical Oncology (2022)

e16026 Background: Gastric carcinoma (GC) is one of the most common cancers with the lowest survival rate in the world. The development from gastritis to GC may be related to genetic factors, but the specific molecular mechanism is not clear. The present study aimed to explore the gene difference between GC and gastritis. Methods: Two gene expression profiles including GC and gastritis were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between GC and gastritis were explored. Through pathway enrichment of DEGs, hub genes were identified. The prognosis significances of hub genes for GC patients were analyzed by overall survival (OS) analysis. Animal models of gastritis and GC were constructed and immunofluorescence and RT-PCR were used to verify the distinct expression of hub genes between the two diseases. Finally, the correlations between hub genes and GC were understood based on BP neural network. Results: A total of 62 DEGs was identified between GC and gastritis. Eight hub genes were identified, including MSLN, FGA, SPP1, THBS2, SPARC, FN1, IGFBP7 and VCAN. Except SPP1, the high expression of the other seven hub genes predicted poor OS for GC patients. In mouse model, the mRNA expression of SPP1, FN1, IGFBP7, THBS2 and VCAN were significantly higher in GC group than that in gastritis group. No matter in mouse model or in Human Protein Atlas, the protein expression of THBS2 and VCAN in GC was higher than that in gastritis. Based on the strong correlation among THBS2, VACN and GC suggested by BP neural network, it was speculated that the expression levels of THBS2 and VACN may be a predictor of GC. Conclusions: Compared with gastritis, THBS2 and VACN are highly expressed in GC. THBS2 and VACN may be potential biomarkers and therapeutic targets for GC.